Synthesis of alkyl cyclopentyl ketones

ABSTRACT

Pyrolysis of trans-1-hydroxy-2-acetoxycyclohexanes to produce alkyl cyclopentyl ketones.

United Stites Patent Leffingwell et al. 1 Sept. 5, 1972 [54] SYNTHESISOF ALKYL CYCLOPENTYL KETONES [56] References Cited [72] Inventors: JohnC. Leffingwell; Ronnld E. UN STATES PATENTS ggf f g'g wmsmn' 2,945,0687/1960 Booth ..260/587 2,972,632 7 2/1961 Bain et al ..260/587 [73]Assignee: R. J. Reynolds Tobacco Company 2,803,647 -8/ I957 Bain et a1..260/489 Winston-Salem, NC. 3,510,510 5/1970 Kropp ..260/489 [22]Filed: March 1969 Primary Examiner-Leon Zitver [21] APPL 07 120Assistant Examiner-Norman Morgenstem Att0rneyPendleton, Neuman, Williams8; Anderson [52] US. Cl ..260/586 R, 252/522, 260/489, 57] ABSTRACT [51,C. ..".f...f...7.8% 73!i;700 to [58] Field of Search ..260/586 587, 488R, 489, y W pemy emnes' 260/617 R 5 Claims, No Drawings SYNTHESIS OFALKYL CYCLOPENTYL KETONES This invention relates to a process forproducing alkyl cyclopentyl ketones.

We have found that alkyl cyclopentyl ketones are obtained by vapor phasepyrolysis of certain trans-lhydroxy-Z-acetoxycyclohexanes.

In accordance with our discovery certain trans-1-hydroxy-Z-acetoxycyclohexanes are subjected to vapor phase pyrolysis attemperatures of approximately 400 C. to 550 C., preferably 425 C. to 475C., with the formation of alkyl cyclopentyl ketones which are thenrecovered. The alkyl cyclopentyl ketones have desirable olfactorycharacteristics and can be used in compounding perfumeries. The use inperfumeries of alkyl cyclopentyl ketones of the type produced inaccordance with this invention is disclosed, for example, in US. Pat.No. 2,946,823 which issued July 26, 1960.

The synthesis of this invention can be illustrated R methyl orisopropyl;

R methyl, isopropyl or isopropenyl;

R" hydrogen; and

R R" dimethylmethylene; with the hydroxyl and acetate groups being intrans position with respect to one another as indicated by the bonds andand R and R being in trans or cis position with respect to one anotheras indicated by the bonds As seen in the above reaction, an allylicalcohol (11) is also formed by pyrolysis. The alkyl cyclopentyl ketone(I) can be separated from the allylic alcohol by fractionaldistillation, chromatography and the like.

The following examples further illustrate but do not limit the presentinvention. All temperatures recited are in degrees centigrade and allparts are by weight unless otherwise stated.

In the following examples, the pyrolysis apparatus employed consisted ofa vertical tube, 18 inch long and 1 inch diameter filled with A inchglass helices, mounted in a combustion furnace. The sample was directedthrough the apparatus by means of a pressure equalizing funnel mountedon the top of the pyrolysis tube. The sample was carried through thepyrolysis tube by gravity and the pressure due to vaporization. Theeffluent pyrolyzate was condensed by means of a cold water condenser andtrapped in an ice cooled vessel. The samples used in pyrolysis were 20percent hydroxyacetates by weight in acetone (a solvent being employedfor convenience but not required). A drop rate of 0.5-2.0 drops/secondwas generally employed. The reaction temperatures reported are externalwall temperatures of the pyrolysis tube. After pyrolyses were complete,the samples were neutralized with a sodium bicarbonate solution andextracted with either hexane or ether. Multiple vapor phasechromatographic analyses were done on each sample using a 10 foot, 10percent diethyleneglycolsuccinate column under several conditions.Product analyses were done by comparison of the retention times andspectra with known samples, when available.

EXAMPLE I TABLE I Pyrolysis of 4-Hydroxyneomenthylacetate PyrolysisAcetate Product Ratio Temperature Pyrolyzed Ketone Allylic Alcohol"Isopropyl 3-methylcyclopentyl ketone trans-2-Menthene-4-ol Theisopropyl 3-methylcyclopentyl ketone was identified from itscharacteristic spectral data. The infrared spectrum exhibited a ketonecarbonyl at 5.83 1.. The nuclear magnetic resonance spectrum exhibited adoublet methyl at 9.01 'r (J E 7 cps, 3H); the isopropyl methylsappeared as a doublet at 8.95 'r (J 7 cps, 6H); the isopropyl protonadjacent to the carbonyl appeared as a 5 peaked multiplet at 7.40 1'(ll-I) and the ring proton adjacent to the ketone carbonyl appeared asunresolved multiplet at 7.0 1- (lI-I). The mass spectrum gave a parentmolecular ion at m/e 154. From the isotopic abundance ratio of M, M 1and M 2 (11.143, 7.68, 14.50 respectively) a molecular weight of154.1851 (calculated mol. wt. 154.2) was determined. Major fragmentpeaks appeared at m/e 154, 111, 99, 83, 71, 66, 55, 43 and 41 withmetastable peaks at m/e 62.1 (due to 111 83) and 36.4 (due to 83 55).Identification of trans-2-menthene-4-ol was made by spectral comparisonwith a known sample.

EXAMPLE II Pyrolysis of l-I-Iydroxyneocarvomenthylacetate1-l-Iydroxyneocarvomenthylacetate is prepared by acetylation ofl-hydroxyneocarvomenthol. The results of pyrolysis thereof at differenttemperatures are tabulated below.

TABLE I1 Pyrolysis of 1Hydroxyneocarvomenthylacetate CyclopropylParticipation in the Carane System", J. Am. Chem. Soc., 88, 4926 (1966).The results of the pyrolysis are tabulated below:

Pyrolysis Acetate Product Ratio Temperature Pyrolyzed Ketone' AllylicAlcohol 5 TAB LE IV Pyrolysis of 3,8-Hydroxy-4a-Acetoxycarane 417- 20 227s 438 79 22 78 Pyrolysis Acetate Product Ratio 449 94 23 77 TemperaturePyrolyzed Ketone" Alcohol 3-1sopropylcyclopentyl methyl ketone 75 24 76trans-Z-Menthene-l-ol 2 0 95 24 76 Identification of thetrans-2-methen-1-ol was made by :38: :88 comparison with a known sample.The 3-isopropy1- cyclopentyl methyl ketone was identified by its charac-,Dimethyl 3 acetyl bicyclo I3 l '0] hexane teristic spectra andsemicarbazone. The infrared spectrum of this ketone exhibited asaturated carbonyl absorption at 5.83 p.. The nuclear magnetic resonancespectrum had resonance signals at 9.12 'r (doublet, .1 6 cps, 611), anacetyl methyl at 7.95 r (singlet, 3H) and the ring proton adjacent tothe carbonyl appeared at 7.13 1- (multiplet, 11-1). The mass spectrumexhibited a molecular ion at m/e 154; other fragment peaks appeared atm/e 139, 136, 111, 96, 84, 71, 69, 55, 43, 41 and a metastable peak at120.1 corresponding to the m/e 154 136 transformation. The semicarbazonemelted at 156-158 [reported literature m.p. 156l5 7].

EXAMPLE 111 Pyrolysis of l-l-lydroxyneoisocarvomenthylacetate1-1-1ydroxyneoisocarvomenthylacetate (c1 28. 1, n 1.4651) was preparedby acetylation of l-hydroxyneoisocarvomenthol (5 g., m.p. 8586, [01],;2.4l) with acetic anhydride.

The results of the pyrolysis are tabulated below.

TABLE 111 Pyrolysis of 1-1-1ydroxyneoisocarvomenthylacetate PyrolysisAcetate Product Ratio Temperature Pyrolyzed Ketone* Allylic Alcohol*3-lsopropylcyclopentyl methyl ketone cis-2-Menthene-l-ol Productidentification was made by trapping the two product peaks viapreparative gas phase chromatography. The first product peak eluting wasidentified as 3-isopropylcyclopentyl methyl ketone by comparison of theinfrared, nuclear magnetic resonance and mass spectra with that of asample previously identified from Example 11. The second minor componentwas identified as cis-2-methen-1-o1 from its characteristic spectra. Theinfrared spectrum exhibited absorptions at 2.97, 3.34, 3.40, 3.45, 6.84,7.25, 7.33 (doublet), 7.53, 8.15-8.37, 8.58, 8.92 (strong), 9.47, 10.22,10.58, 10.90, 11.65, 12.30, 12.45, 13.50 and 13.90 microns. The nuclearmagnetic resonance spectrum exhibited doublet isopropyl methyls centeredat 9.1 1' (J E 6 cps, 6H), a singlet methyl at 8.74 1' (3H), saturatedmethylene protons at 8.1-8.8 'r and an unresolved singlet for theolefinic protons at 4.38 1' (21-1).

EXAMPLE 1V Pyrolysis of 3,8-1-1ydroxy-4a-acetoxycarane3B-Hydroxy-4a-acetoxycarane (m.p. 69.5-70.5) was prepared according tothe procedure of Kropp trans-4,8-mMenthadiene-lol The two pyrolysisproducts were isolated by preparative gas phase chromatography andidentified by their characteristic spectra. The first product peakeluting off a 10 foot 10 percent Carbowax 20M (A inchanalytical) columnwas 6,6-dimethyl-3-acetyl-bicyclo-[ 3.l.0]-hexane, identified by itscharacteristic spectra. The ketone exhibited infrared absorptions at3.31 (cyclopropyl C1-1), 3.40, 3.48, 5.83 (methyl ketone carbonyl),6.85, 7.00, 7.25, 7.35, 8.23, 8.40, 8.87, 11.87 and 12.6 microns. Thenuclear magnetic resonance spectrum exhibited resonance signals at 9.051' (singlet, 61-1) corresponding to the cyclopropyl gem methyl groups,cyclopropyl protons at 8.83 r (multiplet, 21-1) and an acetyl methyl at7.9 1- (singlet, 31-1); the ring proton adjacent to the carbonylappeared at 7.28 as a multiplet (1H). The mass spectrum exhibited amolecular ion at m/e 152 with other fragments at m/e 137,119,109, 95, 93and 91.

The second product peak eluting on preparative vapor phasechromatography solidified and, when sublimed onto a microscope slidecover, melted at 6566. This material was identified as the sylvestrenederivative trans-4,8-m-menthadien- 1 ol from knowledge of theconfiguration of the starting hydroxyacetate coupled with the observedspectral data. The infrared spectrum exhibited a strong Ol-l absorptionat 3.05 L and other absorptions at 3.32, 3.43, 3.50, 6.06 (strong,olefinic), 6.85, 7.26, 7.48, 7.56, 7.75, 7.85,

(broad multiplet, 1H); the terminal methylene protons appeared as apoorly resolved quartet at 5.20 1- (2H) and the ring olefinic protonsappeared at an unresolved singlet at 4.38 T (211) in CDCl;, solution.The mass spectrum exhibited a molecular ion at m/e 152 and other majorfragments at m/e 137, 134, 119, 109, 94 and 79.

EXAMPLE V Pyrolysis of 1Hydroxyneodihydrocarvylacetate1Hydroxyneodihydrocarvylacetate was passed (neat) through the pyrolysiscolumn described above at about 480 C. with a drop rate of -0.5/sec. Thepyrolyzate obtained was -40 percent pyrolysis products and -60 percentunpyrolyzed hydroxyacetate. Distillation gave a fraction boiling at60-72 L/ 1.5 millimeters of mercury which consisted of the mainpyrolysis products. Vapor phase chromatography showed only a single peakon several different columns, but the infrared spectrum exhibited asignificant carbonyl at 5.83 p. indicating the presence of a ketone.Nuclear magnetic resonance spectral analysis indicated the sample to bea mixture of -6S-70 percent 2,8- menthadien-l-ol and -30-35 percent of aketone which was identified as 3-isopropenylcyclopentyl methyl ketone.

It will be understood that in practicing the present invention opticallyactive products are obtained from optically active starting materialsand racemic products from racemic starting materials.

Those modifications and equivalents which fall within the spirit of theinvention are to be considered a part thereof.

We claim:

1. A process which comprises pyrolyzing at a temperature of from about400 C. to 550 C. in vapor phase a compound of the formula wherein Rmethyl or isopropyl;

R methyl, isopropyl or isopropenyl;

R" hydrogen; and

R R diemthylmethylene; treating the pyrolysis products with a base toeffect neutralization of acidic components and recovering an alkylcyclopentyl ketone from said products.

2. A process in accordance with claim 1 wherein 4-hydroxyneomenthylacetate is pyrolyzed and isopropyl 3-methylcyclopentylketone is recovered.

3. A process in accordance with claim 1 whereinlhydroxyneocarvomenthylacetate is pyrolyzed and 3- isopropylcyclopentylmethyl ketone is recovered.

4. A process in accordance with claim 1 whereinlhydroxyneoisocarvomenthylacetate is pyrolyzed and 3-isopropylcyclopentyl methyl ketone is recovered.

5. A process in accordance with claim 1 wherein 3B-hydroxy-4aacetoxycarane is pyrolyzed and 6,6-dimethyl-3-acetyl-bicyclo-[3. l .0]-hexane is recovered.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTIGN Patent No. 3 689,562 Dated s t b 5 922 Inventor(s) John C. Leffingwell and Ronald E.Shackelford It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below:

Column 2, line 37 in the table under the heading "1, Ketone,

"60" should be directly under "65 Column 3, line 5, the last columnheading in the table, before "Allylic" insert Z,

line 7, "78" appearing under the heading "2, Ketone" should be under thecolumn heading. "Allylic Alcohol" directly in line with the numbers and11 1! I 4 lines 27 and I 28, "l57"]' should all be on the same line.

Column 5, lines 5 and 6, "60-72L/l.5" should be 60-72/1.5

Column 6, lines 1-7, the formula should read as follows:

R OH O H V O-C-CH3 line 12, "diemthylmethylene" should bedimethylmethylene line 26, 'hydroxylozacetoxycarane" should be hydroxyla-acetoxycarane (SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT COTTSCHALK Attesting Officer Commissionerof Patents FORM PO-1050 (10-69) 1 USCOMM DC Goa-76,

i u.s. GOVERNMENT rnm'rms omc: In: O-fliidll

2. A process in accordance with claim 1 wherein4-hydroxyneomenthylacetate is pyrolyzed and isopropyl3-methylcyclopentyl ketone is recovered.
 3. A process in accordance withclaim 1 wherein 1-hydroxyneocarvomenthylacetate is pyrolyzed and3-isopropylcyclopentyl methyl ketone is recovered.
 4. A process inaccordance with claim 1 wherein 1-hydroxyneoisocarvomenthylacetate ispyrolyzed and 3-isopropylcyclopentyl methyl ketone is recovered.
 5. Aprocess in accordance with claim 1 wherein 3 Beta -hydroxy-4 Alphaacetoxycarane is pyrolyzed and6,6-dimethyl-3-acetyl-bicyclo-(3.1.0)-hexane is recovered.